1887

Abstract

Resistance to antibiotics is leading to challenges in the treatment of microbial diseases. One amongst the various approaches to control these pathogens is quorum sensing (QS), which is used to rectify resistance issues. Blocking the bacterial QS circuit is the most reliable anti-virulence therapy to control pathogenicity-associated genes. is a contagious bacterium that proliferates in the host by using signalling molecules like acyl-homoserine lactones; these molecules generate and disseminate toxins and virulence factors for increasing host infection.

The herb is known to have antimicrobial, antidiabetic, anti-inflammatory, antitumor medicinal properties amongst others. We hypothesize that its crude extracts will inhibit the QS circuit of (.

The research work was aimed at evaluating anti-quorum sensing and anti-biofilm activity of various crude extracts from against .

Various extraction methods and solvents were availed for maximum separation, and the extracts were screened for anti-quorum sensing activity. The most potent Fruit Ethyl acetate (FEE) extract at non-inhibitory concentrations was found to interrupt both short-chain (RhlI/R) and long-chain (LasI/R) QS circuits and other virulence factors (<0.05) such as elastase, protease, rhamnolipids and pyocyanin levels in . Biofilm inhibitory properties of FEE were demonstrated using atomic force microscopy, scanning electron microscope and confocal laser microscope. infection model (Paralytic assay) was developed to determine the protective role of FEE by reducing the pathogenicity of .

The study results suggest that hot crude FEE extract interfered in the QS circuit, leading to comprehensive debilitation of QS-controlled virulence factors. The extract reduced virulence factor production in at 4 mg ml concentration whilst paradoxically promoting biofilm formation. Possibly, higher sugar content in the extract promoted clump formation of biofilm architecture by increasing exopolysaccharide production. Moreover, analysis of bacterial pathogenesis on reveals a drastic increase in survival rates in FEE treated worms compared to untreated control.

FEE showed promising QS inhibitory activity against . In the future, additional purification of crude FEE is required to remove carbohydrates, and pure isolated phytochemicals from FEE could be used as therapeutic agents to control QS-mediated infections in .

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2023-02-14
2024-05-21
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References

  1. Tanwar J, Das S, Fatima Z, Hameed S. Multidrug resistance: an emerging crisis. Interdiscip Perspect Infect Dis 2014; 2014:1–7 [View Article] [PubMed]
    [Google Scholar]
  2. Knopp M, Andersson DI. Predictable phenotypes of antibiotic resistance mutations. mBio 2018; 9:1–14 [View Article] [PubMed]
    [Google Scholar]
  3. Dzidic S, Bedeković V. Horizontal gene transfer-emerging multidrug resistance in hospital bacteria. Acta Pharmacol Sin 2003; 24:519–526 [PubMed]
    [Google Scholar]
  4. Sun J, Deng Z, Yan A. Bacterial multidrug efflux pumps: mechanisms, physiology and pharmacological exploitations. Biochem Biophys Res Commun 2014; 453:254–267 [View Article] [PubMed]
    [Google Scholar]
  5. Rutherford ST, Bassler BL. Bacterial quorum sensing: its role in virulence and possibilities for its control. Cold Spring Harb Perspect Med 2012; 2:1–25 [View Article] [PubMed]
    [Google Scholar]
  6. Fuqua C, Parsek MR, Greenberg EP. Regulation of gene expression by cell-to-cell communication: acyl-homoserine lactone quorum sensing. Annu Rev Genet 2001; 35:439–468 [View Article]
    [Google Scholar]
  7. Wagner VE, Bushnell D, Passador L, Brooks AI, Iglewski BH. Microarray analysis of Pseudomonas aeruginosa quorum-sensing regulons: effects of growth phase and environment. J Bacteriol 2003; 185:2080–2095 [View Article]
    [Google Scholar]
  8. Majik MS, Parvatkar PT. Next generation biofilm inhibitors for Pseudomonas aeruginosa: synthesis and rational design approaches. Curr Top Med Chem 2014; 14:81–109 [View Article]
    [Google Scholar]
  9. Bonomo RA, Szabo D. Mechanisms of multidrug resistance in Acinetobacter species and Pseudomonas aeruginosa. Clin Infect Dis 2006; 43 Suppl 2:S49–56 [View Article]
    [Google Scholar]
  10. Lister PD, Wolter DJ, Hanson ND. Antibacterial-resistant Pseudomonas aeruginosa: clinical impact and complex regulation of chromosomally encoded resistance mechanisms. Clin Microbiol Rev 2009; 22:582–610 [View Article]
    [Google Scholar]
  11. Parsek MR, Greenberg EP. Acyl-homoserine lactone quorum sensing in gram-negative bacteria: a signaling mechanism involved in associations with higher organisms. Proc Natl Acad Sci U S A 2000; 97:8789–8793 [View Article] [PubMed]
    [Google Scholar]
  12. de Kievit TR, Iglewski BH. Bacterial quorum sensing in pathogenic relationships. Infect Immun 2000; 68:4839–4849 [View Article] [PubMed]
    [Google Scholar]
  13. Waters CM, Bassler BL. Quorum sensing: cell-to-cell communication in bacteria. Annu Rev Cell Dev Biol 2005; 21:319–346 [View Article] [PubMed]
    [Google Scholar]
  14. Welsh MA, Blackwell HE. Chemical genetics reveals environment-specific roles for quorum sensing circuits in Pseudomonas aeruginosa. Cell Chem Biol 2016; 23:361–369 [View Article] [PubMed]
    [Google Scholar]
  15. Miller MB, Skorupski K, Lenz DH, Taylor RK, Bassler BL. Parallel quorum sensing systems converge to regulate virulence in Vibrio cholerae. Cell 2002; 110:303–314 [View Article] [PubMed]
    [Google Scholar]
  16. Lee J, Zhang L. The hierarchy quorum sensing network in Pseudomonas aeruginosa. Protein Cell 2015; 6:26–41 [View Article]
    [Google Scholar]
  17. Moradali MF, Ghods S, Rehm BHA. Pseudomonas aeruginosa lifestyle:a paradigm for adaptation, survival, and persistence. Front Cell Infect Microbiol 2017; 7:39 [View Article]
    [Google Scholar]
  18. Rahman MRT, Lou Z, Yu F, Wang P, Wang H. Anti-quorum sensing and anti-biofilm activity of Amomum tsaoko (Amommum tsao-ko Crevost et Lemarie) on foodborne pathogens. Saudi J Biol Sci 2017; 24:324–330 [View Article]
    [Google Scholar]
  19. Ganesh PS, Rai VR. Journal of traditional and complementary medicine attenuation of quorum-sensing-dependent virulence factors and bio fi lm formation by medicinal plants against antibiotic resistant Pseudomonas aeruginosa. J Tradit Chinese Med Sci 2017; 0–7:
    [Google Scholar]
  20. Soković M, Ćirić A, Glamočlija J, Nikolić M, van Griensven LJLD. Agaricus blazei hot water extract shows anti quorum sensing activity in the nosocomial human pathogen Pseudomonas aeruginosa. Molecules 2014; 19:4189–4199 [View Article]
    [Google Scholar]
  21. Vasavi HS, Arun AB, Rekha PD. Anti-quorum sensing activity of flavonoid-rich fraction from Centella asiatica L. against Pseudomonas aeruginosa PAO1. J Microbiol Immunol Infect 2016; 49:8–15 [View Article] [PubMed]
    [Google Scholar]
  22. Ouedraogo V, Kiendrebeogo M. Methanol extract from anogeissus leiocarpus (DC) Guill. et Perr. (Combretaceae) stem bark quenches the quorum sensing of Pseudomonas aeruginosa PAO1. Medicines 2016; 3:26 [View Article]
    [Google Scholar]
  23. Ahmed AA, Salih FA. Quercus infectoria gall extracts reduce quorum sensing-controlled virulence factors production and biofilm formation in Pseudomonas aeruginosa recovered from burn wounds. BMC Complement Altern Med 2019; 19:1–11 [View Article] [PubMed]
    [Google Scholar]
  24. Zhong L, Ravichandran V, Zhang N, Wang H, Bian X et al. Attenuation of Pseudomonas aeruginosa quorum sensing by natural products: virtual screening, evaluation and biomolecular interactions. Int J Mol Sci 2020; 21:E2190 [View Article] [PubMed]
    [Google Scholar]
  25. Al-Yousef HM, Ahmed AF, Al-Shabib NA, Laeeq S, Khan RA et al. Onion peel ethylacetate fraction and its derived constituent quercetin 4’-O-β-D glucopyranoside attenuates quorum sensing regulated virulence and biofilm formation. Front Microbiol 2017; 8:1–10 [View Article] [PubMed]
    [Google Scholar]
  26. Husain FM, Ahmad I, Al-Thubiani AS, Abulreesh HH, AlHazza IM et al. Leaf Extracts of Mangifera indica L. inhibit quorum sensing - regulated production of virulence factors and biofilm in test bacteria. Front Microbiol 2017; 8:1–12 [View Article]
    [Google Scholar]
  27. Qais FA, Khan MS, Ahmad I. Broad-spectrum quorum sensing and biofilm inhibition by green tea against gram-negative pathogenic bacteria: eciphering the role of phytocompounds through molecular modelling. Microb Pathog 2019; 126:379–392 [View Article]
    [Google Scholar]
  28. Sarkar R, Chaudhary SK, Sharma A, Yadav KK, Nema NK et al. Anti-biofilm activity of marula - a study with the standardized bark extract. J Ethnopharmacol 2014; 154:170–175 [View Article]
    [Google Scholar]
  29. Jadaun V, Prateeksha P, Singh BR, Paliya BS, Upreti DK et al. Honey enhances the anti-quorum sensing activity and anti-biofilm potential of curcumin. RSC Adv 2015; 5:71060–71070 [View Article]
    [Google Scholar]
  30. Das MC, Sandhu P, Gupta P, Rudrapaul P, De UC et al. Attenuation of Pseudomonas aeruginosa biofilm formation by vitexin: a combinatorial study with azithromycin and gentamicin. Sci Rep 2016; 6:23347 [View Article]
    [Google Scholar]
  31. Zhou J-W, Luo H-Z, Jiang H, Jian T-K, Chen Z-Q et al. Hordenine: a novel quorum sensing inhibitor and antibiofilm agent against Pseudomonas aeruginosa. J Agric Food Chem 2018; 66:1620–1628 [View Article] [PubMed]
    [Google Scholar]
  32. Danaraj J, Mariasingarayan Y, Ayyappan S, Karuppiah V. Seagrass Halodule pinifolia active constituent 4-methoxybenzioic acid (4-MBA) inhibits quorum sensing mediated virulence production of Pseudomonas aeruginosa. Microb Pathog 2020; 147:104392 [View Article] [PubMed]
    [Google Scholar]
  33. Peng L-Y, Yuan M, Cui Z-Q, Wu Z-M, Yu Z-J et al. Rutin inhibits quorum sensing, biofilm formation and virulence genes in avian pathogenic Escherichia coli. Microb Pathog 2018; 119:54–59 [View Article] [PubMed]
    [Google Scholar]
  34. Parai D, Banerjee M, Dey P, Chakraborty A, Islam E et al. Effect of reserpine on Pseudomonas aeruginosa quorum sensing mediated virulence factors and biofilm formation. Biofouling 2018; 34:320–334 [View Article] [PubMed]
    [Google Scholar]
  35. Gala VC, John NR, Bhagwat AM, Datar AG, Kharkar PS et al. Attenuation of quorum sensing-regulated behaviour by Tinospora cordifolia extract & identification of its active constituents. Indian J Med Res 2016; 144:92–103 [View Article] [PubMed]
    [Google Scholar]
  36. Shah MD, Kharkar PS, Sahu NU, Peerzada Z, Desai KB. Potassium 2-methoxy-4-vinylphenolate: a novel hit exhibiting quorum-sensing inhibition in Pseudomonas aeruginosa via LasIR/RhlIR circuitry. RSC Adv 2019; 9:40228–40239 [View Article]
    [Google Scholar]
  37. Jothy SL, Zakaria Z, Chen Y, Lau YL, Latha LY et al. Bioassay-directed isolation of active compounds with antiyeast activity from a Cassia fistula seed extract. Molecules 2011; 16:7583–7592 [View Article]
    [Google Scholar]
  38. Iqbal I, Afzal M, Aftab MN, Manzoor F, Kaleem A et al. Hepatotoxicity of cassia fi stula extracts in experimental chicks and assessment of clinical parameters; 2016; 43135–141
  39. Kulkarni A, Govindappa M, Cp C, Ramachandra YL, Koka PS. Phytochemical analysis of cassia fistula and its in vitro antimicrobial, antioxidant activities; 2015; 38–17
  40. Kamath BR, Kizhedath S. In vitro study on antioxidant activity of methanolic leaf extract of cassia fistula Linn. Int J Basic Clin Pharmacol 2018; 7:849 [View Article]
    [Google Scholar]
  41. Gala V, John N, Desai K. Evaluation of the potential of five medicinal plants to inhibit acyl homoserine lactone based quorum sensing in Pseudomonas aeruginosa and Acinetobacter baumannii. Int J Pharma Bio Sci 2013; 4:445–453
    [Google Scholar]
  42. Sasidharan S, Chen Y, Saravanan D, Sundram KM, Yoga Latha L. Extraction, isolation and characterization of bioactive compounds from plants’ extracts. African journal of traditional, complementary, and alternative medicines 2011; 8:1–10 [PubMed]
    [Google Scholar]
  43. Adonizio AL, Downum K, Bennett BC, Mathee K. Anti-quorum sensing activity of medicinal plants in southern Florida. J Ethnopharmacol 2006; 105:427–435 [View Article] [PubMed]
    [Google Scholar]
  44. Heidari A, Noshiranzadeh N, Haghi F, Bikas R. Inhibition of quorum sensing related virulence factors of Pseudomonas aeruginosa by pyridoxal lactohydrazone. Microb Pathog 2017; 112:103–110 [View Article] [PubMed]
    [Google Scholar]
  45. Kalia M, Yadav VK, Singh PK, Sharma D, Pandey H et al. Effect of cinnamon oil on quorum sensing-controlled virulence factors and biofilm formation in Pseudomonas aeruginosa. PLoS One 2015; 10:1–18 [View Article]
    [Google Scholar]
  46. Rajkumari J, Borkotoky S, Murali A, Suchiang K, Mohanty SK et al. Attenuation of quorum sensing controlled virulence factors and biofilm formation in Pseudomonas aeruginosa by pentacyclic triterpenes, betulin and betulinic acid. Microb Pathog 2018; 118:48–60 [View Article] [PubMed]
    [Google Scholar]
  47. Luo J, Kong J-L, Dong B-Y, Huang H, Wang K et al. Baicalein attenuates the quorum sensing-controlled virulence factors of Pseudomonas aeruginosa and relieves the inflammatory response in P. aeruginosa-infected macrophages by downregulating the MAPK and NFκB signal-transduction pathways. Drug Des Devel Ther 2016; 10:183–203 [View Article] [PubMed]
    [Google Scholar]
  48. Krishnan T, Yin W-F, Chan K-G. Inhibition of quorum sensing-controlled virulence factor production in Pseudomonas aeruginosa PAO1 by Ayurveda spice clove (Syzygium aromaticum) bud extract. Sensors (Basel, Switzerland) 2012; 12:4016–4030 [View Article] [PubMed]
    [Google Scholar]
  49. Kim HS, Lee SH, Byun Y, Park HD. 6-gingerol reduces pseudomonas aeruginosa biofilm formation and virulence via quorum sensing inhibition. Sci Rep 2015; 5:8656 [View Article]
    [Google Scholar]
  50. Alain F, Juan LR. Pseudomonas aeruginas-methods & protocols-methods in molecular biology 1149. In Pseudomonas Methods and Protocols-Humana Press 2014
    [Google Scholar]
  51. Bala A, Kumar R, Harjai K. Inhibition of quorum sensing in Pseudomonas aeruginosa by azithromycin and its effectiveness in urinary tract infections. J Med Microbiol 2011; 60:300–306 [View Article]
    [Google Scholar]
  52. Packiavathy I, Priya S, Pandian SK, Ravi AV. Inhibition of biofilm development of uropathogens by curcumin - an anti-quorum sensing agent from Curcuma longa. Food Chem 2014; 148:453–460 [View Article]
    [Google Scholar]
  53. Rajkumari J, Borkotoky S, Murali A, Busi S. Anti-quorum sensing activity of Syzygium jambos (L.) alston against Pseudomonas aeruginosa PAO1 and identification of its bioactive components. South African Journal of Botany 2018; 118:151–157 [View Article]
    [Google Scholar]
  54. Singh VK, Mishra A, Jha B. Anti-quorum sensing and anti-biofilm activity of Delftia tsuruhatensis extract by attenuating the quorum sensing-controlled virulence factor production in Pseudomonas aeruginosa. Front Cell Infect Microbiol 2017; 7:1–16 [View Article] [PubMed]
    [Google Scholar]
  55. Sasidharan S, Chen Y, Saravanan D, Sundram K, Latha L. Extraction, isolation and characterization of bioactive compounds from plants’ Extracts. Afr J Trad Compl Alt Med 2010; 8:1–10 [View Article]
    [Google Scholar]
  56. Syed MH, Yasmeen A, Hussain MS, Subramanian NS, Ramadevi M. Preliminary phytochemical screening and HPTLC fingerprinting of leaf extracts of Pisonea aculeata. Journal of Pharmacognosy and Phytochemistry 2013; 2:36–42
    [Google Scholar]
  57. Chewchinda S, Sithisarn P, Gritsanapan W. Rhein content in cassia fistula pod pulp extract determined by hplc and tlc-densitometry in comparison; 2014; 28409–411
  58. Mahajan-Miklos S, Tan MW, Rahme LG, Ausubel FM. Molecular mechanisms of bacterial virulence elucidated using a Pseudomonas aeruginosa-Caenorhabditis elegans pathogenesis model. Cell 1999; 96:47–56 [View Article] [PubMed]
    [Google Scholar]
  59. Darby C, Cosma CL, Thomas JH, Manoil C. Lethal paralysis of Caenorhabditis elegans by Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 1999; 96:15202–15207 [View Article] [PubMed]
    [Google Scholar]
  60. Journal I, Sciences P. Cassia fistula linn: a review of phytochemical and pharmacological. IJPSR 2014; 5: [View Article]
    [Google Scholar]
  61. Hurley MN, Cámara M, Smyth AR. Novel approaches to the treatment of Pseudomonas aeruginosa infections in cystic fibrosis. Eur Respir J 2012; 40:1014–1023 [View Article]
    [Google Scholar]
  62. Tan P-W, Tan W-S, Yunos NYM, Mohamad NI, Adrian T-G-S et al. Short chain N-acyl homoserine lactone production in tropical marine Vibrio sinaloensis strain T47. Sensors (Basel) 2014; 14:12958–12967 [View Article]
    [Google Scholar]
  63. Chu W, Zhou S, Jiang Y, Zhu W, Zhuang X et al. Effect of traditional chinese herbal medicine with antiquorum sensing activity on Pseudomonas aeruginosa. Evid Based Complement Alternat Med 2013; 2013:648257 [View Article]
    [Google Scholar]
  64. Kessler E, Safrin M, Gustin JK, Ohman DE. Elastase and the LasA protease of Pseudomonas aeruginosa are secreted with their propeptides. J Biol Chem 1998; 273:30225–30231 [View Article] [PubMed]
    [Google Scholar]
  65. Hoge R, Pelzer A, Rosenau F, Wilhelm S. Weapons of a pathogen: proteases and their role in virulence of Pseudomonas aeruginosa. Curr Res Technol Educ Top Appl Microbiol Microb Biotechnol 2010; 45:383–395
    [Google Scholar]
  66. Vasavi HS, Arun AB, Rekha PD. Anti-quorum sensing activity of Psidium guajava L. flavonoids against Chromobacterium violaceum and Pseudomonas aeruginosa PAO1. Microbiol Immunol 2014; 58:286–293 [View Article] [PubMed]
    [Google Scholar]
  67. Davies DG, Parsek MR, Pearson JP, Iglewski BH, Costerton JW et al. The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science 1998; 280:295–298 [View Article] [PubMed]
    [Google Scholar]
  68. Ueda A, Wood TK. Connecting quorum sensing, c-di-GMP, pel polysaccharide, and biofilm formation in Pseudomonas aeruginosa through tyrosine phosphatase TpbA (PA3885). PLoS Pathog 2009; 5:1–15 [View Article]
    [Google Scholar]
  69. Beauregard PB, Chai Y, Vlamakis H, Losick R, Kolter R. Bacillus subtilis biofilm induction by plant polysaccharides. Proc Natl Acad Sci U S A 2013; 110:E1621–30 [View Article]
    [Google Scholar]
  70. Sandasi M, Leonard CM, Viljoen AM. The in vitro antibiofilm activity of selected culinary herbs and medicinal plants against Listeria monocytogenes. Lett Appl Microbiol 2010; 50:30–35 [View Article]
    [Google Scholar]
  71. Shailajan S, Yeragi M, Tiwari B. Estimation of rhein from Cassia fistula Linn. using validated HPTLC method. Int J Green Pharm 2013; 7:62 [View Article]
    [Google Scholar]
  72. Rajkumari J, Borkotoky S, Murali A, Suchiang K, Mohanty SK et al. Cinnamic acid attenuates quorum sensing associated virulence factors and biofilm formation in Pseudomonas aeruginosa PAO1. Biotechnol Lett 2018; 40:1087–1100 [View Article] [PubMed]
    [Google Scholar]
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